The purpose of this study is to determine the qualitative and quantitative toxicity of intrathecally administered topotecan in a limited dosage escalation schedule and define a safe dose of intrathecally administered topotecan that can be recommended for subsequents phase II studies. Prior studies in nonhuman primates demonstrated the safety and feasibility of intrathecal(IT) administration of topotecan (TPT), an active anticancer drug that inhibits topoisomerase I. We subsequently initiated a phase I trial of IT TPT in patients (pts) >= 3 yr who have refractory meningeal malignancies. TPT is administered twice weekly during a 4-6 week induction, followed by a consolidation phase of 4 weekly doses, twice monthly x 4 mo, and then monthly maintenance doses. The starting dose was 0.025 mg. in the first pt cohort weekly intra-pt dose escalations to 0.05, 0.1, and 0.2 mg were performed. Subsequesnt cohorts have been treated without escalation at 0.2 and 0.4 mg. Twelve pts (5 male), median age 13 yr (range 3-19), with meningeal spread of medulloblastoma/PNET (4). rhabdomyosarcoma (2), gliomatosis (2), retinoblastoma (1), pinealblastoma (1), germinoma (1) and ALL (1) have been treated. Non-dose-limiting toxicities include: nausea, vomiting, and headache. One pt had seizures and hemiparesis that were felt to be disease-related. One pt had an isolated episode of myoclonic jerking and staring after the 3rd dose of IT TPT. three pts have had SD and received IT TPT for > 5 months with stable disease. Peak TPT lactone levels in 3 pts with indwelling Ommaya reservoirs treated at the 0.2 mg dose level were 6.1 and 6.8 micrometers. The terminal t[1/2] was 2.8 h. In summary, IT TPT is well-tolerated at doses of up to 0.4 mg.